Neurodegenerative Disease and REM Behavior Disorder

Abstract

Patients with cerebral degenerative conditions commonly suffer from a variety of sleep disorders, including sleep-disordered breathing, insomnia, parasomnias (REM sleep behavior disorder), circadian rhythm disturbances, and restless legs syndrome. When these sleep disorders go unrecognized and untreated, they can lead to decreased quality of life and worsening neurological symptoms related to the underlying condition. Appropriate management initially requires taking a careful history from the patient and bed partner regarding their sleep. In addition, polysomnography may be required to aid in the diagnosis of sleep-disordered breathing or parasomnias. Occasionally, adjusting the dosages of sedating or sleep disrupting medications and improving sleep hygiene may improve sleep complaints. However, in most cases restoring quality nighttime sleep requires specific therapeutic intervention. In patients that suffer from sleep apnea, this usually means treatment with continuous positive airway pressure (CPAP), positional therapy, dental appliances, upper airway surgery, or weight loss. Pharmacological treatment of insomnia in patients with cerebral degenerative conditions can be difficult due to side effects (worsening balance, cognition) and lack of data in this patient population. Behavioral strategies such as cognitive-behavioral therapy have been effective and are considered safer than hypnotic therapy, but can be limited due to access to trained providers (distance and number of providers) and limited cognitive functioning of the patient. Parasomnias, namely REM sleep behavior disorder, are managed by looking for any underlying cause of arousals (sleep apnea, periodic leg movements of sleep), implementing safety precautions, and pharmacologically with either benzodiazepines or melatonin. Restless legs syndrome may improve with iron replacement or dopamine agonist therapy, as it does in other patient populations. Light therapy may be beneficial in patients suffering from circadian rhythm disorders such as advanced sleep phase syndrome.

Peripheral vascular dysfunction in migraine: a review

“…Several among the available studies did not reveal any alteration in the endothelial function of migraineurs. Six of them did not find any difference in FMD between migraineurs and control subjects (Table  2) [20-23,25,26] and a further study confirmed the lack of any alteration in endothelial function assessed by PAT ratio (Table  3) [32]. Three studies assessing peripheral vasodilation after pharmacological stimuli found comparable responses in subjects with and without migraine (Table  3) [20,33,35].…”

“…Most of them assessed endothelial function by measuring FMD (Table  2) [20-30], some used PAT (Table  3) [31,32], some measured peripheral vasodilation in response to pharmacological stimuli (Table  3) [20,30,33-35], and others assessed endothelial progenitor cells (EPCs) (Table  4) [23,36,37]. Findings were not consistent across the studies.…”

“…In addition, the results of one study suggested that the impaired vascular reactivity in migraineurs is entirely attributable to a reduced response of vascular smooth muscle cells to NO while the endothelial response to NO appeared intact [34]. Some additional studies supported the presence of an endothelial dysfunction in migraineurs by documenting a decreased number of EPCs [23,36] or a higher number of more mature EPCs (which could be associated with potential endothelial damage) in migraineurs (Table  4) [37]. EPCs maintain the integrity of damaged endothelium and are considered a marker of endothelial function [38].…”

“…These biochemical changes may precede structural damage. In particular, alterations in the NO pathway have been described [30,39,40] as well as increased levels of calcitonin gene-related peptide (CGRP), vascular endothelial growth factors (VEGF), von Willebrand factor (vWF) activity, tissue plasminogen activator antigen, C-reactive protein and endothelin-1 [21,23,40]. Recently, a study involving 40 non-hypertensive subjects with migraine without aura randomized to treatment with enalapril 5 mg twice a day for 3 months or to placebo, showed that active treatment was associated with an increase in FMD values [41].…”

Treatment of Dementia With Lewy Bodies

“…Prescribe caffeinated drinks from the morning until early afternoon, but avoid caffeine if the patient has Periodic Leg Movement Disorder of Sleep, or Restless Leg Syndrome [103]. …”